In recent years, the use of Cannabis and Cannabis extracts for medicinal purposes has increased. However, the complex chemical composition of Cannabis and Cannabis extracts presents several complications for medicinal use. First, while some components of Cannabis have medically useful characteristics, other compounds result in the undesirable psychoactive and narcotic effects that limit the medical usefulness of Cannabis in many applications and patients. Further, the mixed composition of plant-based materials (which varies due to strain, cultivation method, preparation, or age) makes safety and efficacy testing difficult, as various compounds may have synergistic or interfering effects. In addition, while numerous compounds in Cannabis have been shown to have medicinal use, a small number of psychoactive compounds from Cannabis are scheduled by the federal government as controlled substances. Without isolated and purified compounds of medicinal value from Cannabis, pharmaceutical usage of specific Cannabis-derived compounds is greatly limited.
The structures of the isoprenoid compounds THCA (also known as 2-COOH-THC) and THC (L19-THCA) are shown in FIG. 1a and FIG. 1b, respectively. THC is the primary psychoactive compound in Cannabis, while THCA is neither psychoactive norfederally scheduled as a controlled substance (Stark, 1990, Marijuana Chemistry: Genetics, Processing, Potency). Academic studies have shown that isolated THCA has a number of medically useful characteristics, such as anti-inflammatory properties, anticancer effects, and antiemetic effects. A table of these studies is shown in FIG. 2.
THC is a chemical degradation product of THCA. FIG. 3 shows the reaction by which THCA is decarboxylated and converted to THC (and carbon dioxide). The reaction shown in FIG. 3 is greatly accelerated by heat; while the THCA is the predominant compound in living and freshly harvested Cannabis, THC is formed rapidly as Cannabis is burned (e.g., by smoking). Small amounts of THC are formed slowly from THCA as Cannabis is dried or aged. In addition to heat instability, the degradation of purified THCA to THC is accelerated by ultraviolet light, oxygen, or acidic conditions (Zoller et al., 2000). Notably, THCA is stable in vivo, as shown by mass spectrometry in a study of THCA metabolism in rat by Jung et al., 2009.
Current methods for purification of THCA from THC involve expensive and time intensive methods that do not scale well, such a high-pressure liquid chromatography. While current THCA purification methods are suitable for the production of analytical or research quantities of THCA, medicinal or pharmaceutical production would require a less expensive and more robust process.
There is currently a lack of data available with respect to the effects of various plant-based medicines, remedies or health-promoting agents—even widely used remedies may not have undergone substantial clinical testing. The lack of data is particularly acute with respect to historically controlled substances, such as Cannabis. The effects of plant-based products may vary significantly between strains, between preparations, and between delivery routes. The lack of highly purified and stable plant based medicinal compounds is one of the primary impediments to meaningful testing of the medicinal properties of these compounds, or to any pharmaceutical use.
There exists an unmet need to develop a method for the rapid extraction of THCA from Cannabis, followed by purification of THCA from THC and other Cannabis compounds, psychoactive or otherwise. There further exists an unmet need that this purification method be inexpensive and robust, so as to be suitable to scaled production. There further exists an unmet need for methods by which the purified THCA may be stabilized to prevent subsequent degradation of THCA to THC.